Genomics of microRNAs

Department of Biological Sciences and Research Center for Functional Cellulomics, Seoul National University, Seoul, 151-742, Korea.
Trends in Genetics (Impact Factor: 9.92). 04/2006; 22(3):165-73. DOI: 10.1016/j.tig.2006.01.003
Source: PubMed


Discovered just over a decade ago, microRNA (miRNA) is now recognized as one of the major regulatory gene families in eukaryotic cells. Hundreds of miRNAs have been found in animals, plants and viruses, and there are certainly more to come. Through specific base-pairing with mRNAs, these tiny approximately 22-nt RNAs induce mRNA degradation or translational repression, or both. Because a miRNA can target numerous mRNAs, often in combination with other miRNAs, miRNAs operate highly complex regulatory networks. In this article, we summarize the current status of miRNA gene mining and miRNA expression profiling. We also review up-to-date knowledge of miRNA gene structure and the biogenesis mechanism. Our focus is on animal miRNAs.

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Available from: Jin-Wu Nam,
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    • "Among the most differentially expressed genes in all PSC derivatives are LIN28A and LIN28B, RNA binding proteins known to regulate the let-7 family of miRNAs (Patterson et al., 2012). LIN28B seems to function primarily in the nucleus by sequestering pri-let-7s to prevent maturation by Microprocessor, whereas LIN28A functions in the cytoplasm by recruiting uridylyl transferase to polyuridylate the pre-let-7s and prevent their further processing by Dicer (Graf et al., 2013; Hagan et al., 2009; Kim and Nam, 2006; Lee et al., 2014; Piskounova et al., 2011). In lower organisms, Lin28A expression is strongly correlated with the differentiation status and self-renewing capacity of cells throughout development. "
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    ABSTRACT: It is clear that neural differentiation from human pluripotent stem cells generates cells that are developmentally immature. Here, we show that the let-7 plays a functional role in the developmental decision making of human neural progenitors, controlling whether these cells make neurons or glia. Through gain- and loss-of-function studies on both tissue and pluripotent derived cells, our data show that let-7 specifically regulates decision making in this context by regulation of a key chromatin-associated protein, HMGA2. Furthermore, we provide evidence that the let-7/HMGA2 circuit acts on HES5, a NOTCH effector and well-established node that regulates fate decisions in the nervous system. These data link the let-7 circuit to NOTCH signaling and suggest that this interaction serves to regulate human developmental progression.
    Stem Cell Reports 10/2014; 3(5). DOI:10.1016/j.stemcr.2014.08.015 · 5.37 Impact Factor
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    • "Although there is no consensus about the most frequent miRNA genomic location in animals due, among other factors, to varying miRNA genomic distribution in different species, there is no doubt that they mainly map to intergenic regions as solo or clustered genes or to intronic regions of defined protein-coding or non-coding transcription units (Bartel, 2004; Kim and Nam, 2006). The most striking deviation was shown in mouse testes, where approximately 30% of the miRNA genes mapped to exonic sequences (Ro et al., 2007). "
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    ABSTRACT: Microribonucleic acids, best known as microRNAs or miRNAs, are small, non-coding RNAs with important regulatory roles in eukaryotic cells. Here, I present a broad review on highly relevant but generally non-depicted features of miRNAs, among which stand out the non-conventional miRNA seed sites, the unusual messenger RNA (mRNA) target regions, the non-canonical miRNA-guided mechanisms of gene expression regulation, and the recently identified new class of miRNA ligands. Furthermore, I address the miRNA uncommon genomic location, transcription, and subcellular localization. Altogether, these unusual features and roles place the miRNA system as a very diverse, complex, and intriguing biological mechanism.
    Frontiers in Genetics 09/2014; 5:337. DOI:10.3389/fgene.2014.00337
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    • "Central to studying miRNA-mediated gene modulation is the clear understanding of their gene structure and biogenesis, which have been described in several reviews [31] [32] [33]. miRNA genes are distributed nonrandomly in human genome, and nearly half of them are found as tandem arrays within clusters, sharing the same promoter, which may indicate gene duplications [15] [34]. "
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    ABSTRACT: Discovered in 1993, micoRNAs (miRNAs) are now recognized as one of the major regulatory gene families in eukaryotes. To date, 24521 microRNAs have been discovered and there are certainly more to come. It was primarily acknowledged that miRNAs result in gene expression repression at both the level of mRNA stability by conducting mRNA degradation and the level of translation (at initiation and after initiation) by inhibiting protein translation or degrading the polypeptides through binding complementarily to 3'UTR of the target mRNAs. Nevertheless, some studies revealed that miRNAs have the capability of activating gene expression directly or indirectly in respond to different cell types and conditions and in the presence of distinct cofactors. This reversibility in their posttranslational gene regulatory natures enables the bearing cells to rapidly response to different cell conditions and consequently block unnecessary energy wastage or maintain the cell state. This paper provides an overview of the current understandings of the miRNA characteristics including their genes and biogenesis, as well as their mediated downregulation. We also review up-to-date knowledge of miRNA-mediated gene upregulation through highlighting some notable examples and discuss the emerging concepts of their associations with other posttranscriptional gene regulation processes.
    International Journal of Plant Genomics 08/2014; 2014:970607. DOI:10.1155/2014/970607
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